CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes

Maria L. Elkjaer, Arkadiusz Nawrocki, Tim Kacprowski, Pernille Lassen, Anja Hviid Simonsen, Romain Marignier, Tobias Sejbaek, Helle H. Nielsen, Lene Wermuth, Alyaa Yakut Rashid, Peter Høgh, Finn Sellebjerg, Richard Reynolds, Jan Baumbach, Martin R. Larsen, Zsolt Illes*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

To identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 proteins selected by comprehensive statistics were quantified in 170 individual CSF samples. (iii) Genes of the identified proteins were also screened among transcripts in 73 MS brain lesions compared to 25 control brains. F-test based feature selection resulted in 8 proteins differentiating the MS subtypes, and secondary progressive (SP)MS was the most different also from controls. Genes of 7 out these 8 proteins were present in MS brain lesions: GOLM was significantly differentially expressed in active, chronic active, inactive and remyelinating lesions, FRZB in active and chronic active lesions, and SELENBP1 in inactive lesions. Volcano maps of normalized proteins in the different disease groups also indicated the highest amount of altered proteins in SPMS. Apolipoprotein C-I, apolipoprotein A-II, augurin, receptor-type tyrosine-protein phosphatase gamma, and trypsin-1 were upregulated in the CSF of MS subtypes compared to controls. This CSF profile and associated brain lesion spectrum highlight non-inflammatory mechanisms in differentiating CNS diseases and MS subtypes and the uniqueness of SPMS.

Original languageEnglish
Article number4132
JournalScientific Reports
Volume11
Number of pages13
ISSN2045-2322
DOIs
Publication statusPublished - 18. Feb 2021

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